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Investigating the Role of an SK Channel Activator on Survival and Motor Function in the SOD1-G93A, ALS Mouse Model

Dancy, Matthew Thomas
http://orcid.org/0000-0002-7798-5907
http://rave.ohiolink.edu/etdc/view?acc_num=wright1493817751768876

Abstract Details

2017, Master of Science (MS), Wright State University, Physiology and Neuroscience.
Amyotrophic Lateral Sclerosis (ALS) is a fatal, adult-onset progressive degenerative motor neuron disease that is characterized by muscle atrophy and weakness due to the loss of upper and lower motor neurons. Average survival time for individuals diagnosed with the disease is three to five years; currently there is no cure and only one drug approved by the Food and Administration (FDA). Scientists have proposed various theories in order to solve the mystery which surrounds ALS. One of these theories hypothesizes how hyperexcitability and excitotoxicity leads to the death of motor neurons. In this study, we will address ways of combatting the effects of hyperexcitability as well as excitotoxicity by targeting a specific channel type. The channels in question are small conductance calcium activated potassium channels (SK channels). We chose to target these channels because they directly affect the medium after-hyperpolarization (mAHP) of the cell which controls firing rate. We postulate that SK channels are being altered in such a way that cell firing rate has been increased, leading to phenotypes associated with the disease such as abnormal excitability, mitochondrial dysfunction, axonal loss motor impairment, muscle atrophy as well as excitotoxicity, thus leading to the spread of motor neuron death. Upon administration with a specific SK channel activator in the form of CyPPA; improvements in motor function and survival were found. These improvements suggest that SK channels are indeed viable drug targets and specific SK channel activators may be treatment options for individuals suffering from ALS.
Sherif Elbasiouny, Ph.D., P.E. (Committee Chair)
Mark Rich, M.D., Ph.D. (Committee Member)
Keiichiro Susuki, M.D., Ph.D. (Committee Member)
101 p.
Behavioral Sciences; Neurobiology; Neurosciences; Physiology
ALS; amyotrophic lateral sclerosis; SK channels; motoneurons; motor neurons; SOD1; potassium channels

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Citations

  • Dancy, M. T. (2017). Investigating the Role of an SK Channel Activator on Survival and Motor Function in the SOD1-G93A, ALS Mouse Model [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1493817751768876

    APA Style (7th edition)

  • Dancy, Matthew. Investigating the Role of an SK Channel Activator on Survival and Motor Function in the SOD1-G93A, ALS Mouse Model. 2017. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1493817751768876.

    MLA Style (8th edition)

  • Dancy, Matthew. "Investigating the Role of an SK Channel Activator on Survival and Motor Function in the SOD1-G93A, ALS Mouse Model." Master's thesis, Wright State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=wright1493817751768876

    Chicago Manual of Style (17th edition)

wright1493817751768876
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© 2017, all rights reserved.
This open access ETD is published by Wright State University and OhioLINK.